Prescribing statins - current concepts

What is the dose of statin that should be prescribed to patients who have clinically evident coronary artery disease?

When a patient below the age of 75 years has evidence of coronary artery disease, statins in appropriately high doses should be prescribed irrespective of their serum cholesterol values. A high dose (or intensive dose) for Atorvastatin refers to 40 to 80mg per day; a similar dose for Simvastatin is 40mg per day.

Is the dose of statin prescribed to a patient determined by the LDL - cholesterol value?
The new 2013 cholesterol lowering guidelines tell us that the decision to start a statin can be determined, in part, by the LDL cholesterol level. But the dose (high intensity versus moderate intensity) is determined by parameters other than the LDL cholesterol value. 

When should serum creatine kinase (CK) be tested when patients are on statins?

CK needs to be tested only when patients on statins complain of muscle pain or muscle weakness.

How can muscle pain due to statins be differentiated from other causes of myalgia?

Myalgia due to statins will resolve within 2 weeks of stopping the drug. When muscle pain persists beyond 2 weeks after discontinuing statins, other causes of myalgia must be considered.

Should liver function tests be done routinely when patients are on statins?

No. It is not necessary.

Should all patients with diabetes be prescribed with a statin?

All diabetic patients between the ages of 40 and 75 years should generally receive a statin unless their LDL cholesterol level is unusually low (below 1.8mmol/L). Whether low dose (moderate intensity) or high dose (high intensity) statins are needed should be decided by their 10-year risk of developing atherosclerotic coronary artery disease.

Is there any role for the combination of a statin with a non-statin (fenofibrate / gemfibrosil / nicotinic acid)?

Yes. There is definite evidence for doing so in patients with familial hypercholesterolemia because the reduction in cardiovascular risk is proportional to the degree of lowering of LDL cholesterol. The diagnosis of familial hypercholesterolemia should be suspected in patients with LDL cholesterol levels more than 4.9mmol/L (190mg/dL). Whether there is a benefit in combining a statin with a non-statin for those with diabetes and coronary artery disease is still not clear. When a statin is combined with a fibrate, it is better to use fenofibrate (and not gemfibrosil) because it is safer.

Can statins be continued during pregnancy?
Statins and non-statin cholesterol lowering drugs are classified as pregnancy category X and should not be taken during pregnancy and while breast feeding. Those who are on statins should discontinue them 2 to 3 months before becoming pregnant. 

Is there an increased risk of new-onset diabetes due to statin therapy?
Yes, but the risk is modest. With low dose statin therapy, 1 out of 1000 will develop diabetes per year. With high dose statin therapy, 3 out of 1000 will develop diabetes per year according to available evidence. On the other hand, appropriately used statin therapy prevents 5 to 6 cases of atherosclerosis induced vascular disease per 1000 population per year. 

Is there any role for using statins for primary prevention in individuals who are younger than 40 years of age if they do not have diabetes or heart disease?
Yes, in selected individuals. Young people who have risk factors like: a strong family history of premature coronary artery disease, an LDL cholesterol more than 4.1mmol/L (160mg/dL), a high sensitivity CRP level more than 2mg/L, or a coronary calcium score more than 300units can be considered for statin therapy as primary prevention. Moderate intensity (lower dose) statins are recommended if their calculated lifetime risk of developing coronary artery disease is not high. High intensity statin therapy is recommended if the calculated lifetime risk is high.

How are the statins different from each other in their LDL- cholesterol lowering ability?
When statins are evaluated based on their ability to lower LDL cholesterol, we note that 5mg of Rosuvastatin is equal to 10mg of Atrovastatin is equal to 20mg of Simvastatin is equal to 40mg of Lovastatin. The relationship between dose of statin and degree of LDL-cholesterol lowering is not linear: doubling of a statin dose does not double the fall in LDL cholesterol, but only an extra 6 percent fall will be seen.

Based on the 2013 cholesterol lowering guidelines from the American Heart Association and the prevention guidelines clinical vignettes . 

Acute and chronic gout

The following is based on the Malaysian Clinical Practice Guidelines for Management of Gout (Published in October 2008)

1. The first line treatment for acute gouty arthritis is non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, diclofenac and indomethacin. Aspirin is not recommended because it increases uric acid levels in the blood unless given in very high doses.

Question: A patient with acute gouty arthritis has peptic ulcer disease and hence cannot be prescribed any of the traditional NSAIDs. What can be done for pain relief in this situation?

Answer: We can use either COX-2 (cyclooxygenase 2) inhibitors like Celecoxib or Etoricoxib. We can also use Colchicine. A third option for pain relief, particularly in elderly people and in those who have renal disease, is the use of glucocorticoids. Short courses of oral prednisolone are effective in providing pain relief. Intra-articular injections of corticosteroids are also helpful.

2. Long term therapy with Allopurinol to reduce serum uric acid levels should be initiated in those who have chronic gout – that is, those who have experienced 3 or more episodes of acute gouty arthritis in a year, those who have erosive gouty arthritis, those who have tophi, and those who have uric acid nephropathy or uric acid stones.

Question: How is Allopurinol prescribed?

Answer: Allopurinol should be started in a low dose of 100 to 150mg once a day. After 3 to 4 weeks, the dose can be increased to usual maximum dose of 300mg per day. In those who have renal impairment, the dose of Allopurinol should be appropriately reduced. For example, if a patient with gout has end stage renal failure, the dose of allopurinol should not exceed 100mg once in 2 to 3 days. If a patient with gout has Stage 3 CKD, the maximum dose should not exceed 200mg per day. The usual dose of 300mg per day should only be prescribed for those with normal renal function.

Question: Can Allopurinol be prescribed for those with asymptomatic hyperuricemia?

Answer: It is not necessary to prescribe Allopurinol for all asymptomatic people with elevated uric acid levels because most of them will never suffer from gout. However, if the uric acid level is very high (about twice the upper limit of normal), it is better to prescribe allopurinol to reduce the risk of developing nephropathy. Prophylactic use of allopurinol is also recommended when a rapid increase in serum uric acid  is anticipated – as in treatment of leukemias and lymphomas.

Question: Since allopurinol has the potential to cause severe allergic reactions and bone marrow depression, is there an alternative drug for reducing serum uric acid?

Answer: Probenecid is also a uric acid lowering drug. Unlike allopurinol, probenecid increases the excretion of uric acid in the urine. Hence probenecid is not recommended for those who have uric acid nephropathy or uric acid nephrolithiasis. Ideally, urinary excretion of uric acid should be measured and probenecid should be prescribed only for those who do not have elevated urinary uric acid levels. 

Question: Will allopurinol therapy increase the risk of acute gouty arthritis?

Answer: Yes, there is an increased risk of acute arthritis during the initial period after allopurinol is initiated. That is why one should not prescribe allopurinol during an acute episode. To minimise acute episodes while initiating allopurinol therapy, low doses of colchicine (0.5mg twice a day) can be given. Colchicine can be stopped when the patient has not suffered acute arthritis for 6 months or when serum uric acid levels are normal for one month.

Question: Should allopurinol be stopped when a person, who is already on allopurinol, develops acute gouty arthritis?

Answer: No. Allopurinol need not be stopped in this situation. 

Question: What is risk when Allopurinol is prescribed along with Ampicillin?

Answer: There is an increased risk of developing a skin rash due to allopurinol.

Question: What is the risk of prescribing allopurinol with warfarin?

Answer: There is the risk of bleeding because allopurinol reduces the metabolism of warfarin and increases its half-life.

3. Polyarticular gout mimics rheumatoid arthritis. Gouty arthritis can lead to osteoarthritis.

Question: How do the subcutaneous tophi in gout differ from the subcutaneous nodules of rheumatoid arthritis?

Answer: Tophi are painless while rheumatoid nodules are generally painful.

Question: Is it possible to differentiate gouty arthritis from osteoarthritis with an x-ray of a painful joint?

Answer: Yes. The joint space is preserved in acute gouty arthritis while the joint space is narrowed in osteoarthritis.

4. A normal serum uric acid in a person with acute arthritis does not exclude gout.

Question: Can a therapeutic response to colchicine be used to diagnose gout?

Answer: Yes. Acute gouty arthritis responds within 48 hours to colchicine.

5. Alcohol should be restricted or avoided in all patients with gout.

Question: Why is alcohol restriction necessary in gout?

Answer: Alcohol reduces the excretion of purines. Uric acid is the result of purine metabolism.

6. Drugs that increase uric acid levels can provoke acute gouty arthritis.

Question: A patient with diabetes, hypertension and ischemic heart disease experiences frequent gouty arthritis. Which of her medications may need to be changed?

Answer: Is she on thiazide diuretics for hypertension and low dose aspirin for heart disease? If yes, these should be changed.

7. Food that is high in purine content should be avoided by those who have gout.

Question: Should eggs be avoided by those who have gout?

Answer: No. Eggs have low purine content.

Question: Should mushrooms, beans and peas be avoided by those who have gout?

Answer: These foods have moderate purine content and should be eaten less frequently than usual.

Question: Can those with gout eat red meat, anchovies and sardines?

Answer: These are food items with high purine content and should be avoided.